A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.
OBJECTIVE
Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels.


METHODS
The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant).


RESULTS
Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration.


CONCLUSIONS
DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.
Bertino
G
G
Department of Internal Medicine and Systemic Diseases, Santa Marta Hospital, University of Catania, Catania, Italy. gaetanobertinounict@libero.it
Ardiri
A M
AM
Boemi
P M
PM
Ierna
D
D
Interlandi
D
D
Caruso
L
L
Minona
E
E
Trovato
M A
MA
Vicari
S
S
Li Destri
G
G
Puleo
S
S
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D015854:Up-Regulation; D014812:Vitamin K / Q000097:blood; D010837:Vitamin K 1 / Q000008:administration & dosage; D014813:Vitamin K Deficiency / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
C097353:AFP protein, human; D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; D014812:Vitamin K; C008208:acarboxyprothrombin; D010837:Vitamin K 1; D011516:Prothrombin